Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24580706 242 GECPVCLLSIQTPTACSVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRIY 295
Cdd:cd16451   1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24580706 242 GECPVCLLSIQTPTACSVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRIY 295
Cdd:cd16451   1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 24580706    246 VCLLSIQTPT--ACSVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRIYE 296
Cdd:smart00504   3 LCPISLEVMKdpVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLIPNLA 55

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 24580706 243 ECPVCLLSIQTPtACSVSGYVFCWKCIVSHM--KEHGTCPV 281
Cdd:COG5574 217 KCFLCLEEPEVP-SCTPCGHLFCLSCLLISWtkKKYEFCPL 256

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24580706 242 GECPVCLLSIQTPTACSVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRIY 295
Cdd:cd16451   1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24580706 246 VCLLSIQTP-TAC--SVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRI 294
Cdd:cd16656   2 VCAISGEVPeEPVvsPKSGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLIEI 53

RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24580706 243 ECPVCLLSIQTP--TACsvsGYVFCWKCIVSHM----KEHGTCPVTHYPISLDDL 291
Cdd:cd16536   2 QCPICLEPPVAPriTRC---GHIFCWPCILRYLslseKKWRKCPICFESIHKKDL 53

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 24580706   243 ECPVCLLSIQTPTACSVS--GYVFCWKCIVSHMKEHGTCPV 281
Cdd:pfam13639   2 ECPICLEEFEEGDKVVVLpcGHHFHRECLDKWLRSSNTCPL 42

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 24580706 242 GECPVCLLSIQTPTACSVSGYVFCWKCIVSHMKEHGT-CPVTHYPIS 287
Cdd:cd16544   3 LTCPVCQEVLKDPVELPPCRHIFCKACILLALRSSGArCPLCRGPVG 49

U-box domain, a modified RING finger, found in peptidyl-prolyl cis-trans isomerase-like 2 (PPIL2) and similar proteins; PPIL2 (EC 5.2.1.8), also known as PPIase, CYC4, cyclophilin-60 (Cyp60), cyclophilin-like protein Cyp-60, or Rotamase PPIL2, is a nuclear-specific cyclophilin which interacts with the proteinase inhibitor eglin c and regulates gene expression. PPIL2 belongs to the cyclophilin family of peptidylprolyl isomerases and catalyzes cis-trans isomerization of proline-peptide bonds, which is often a rate-limiting step in protein folding. It positively regulates beta-site amyloid precursor protein cleaving enzyme (BACE1) expression and beta-secretase activity. Moreover, PPIL2 plays an important role in the translocation of CD147 to the cell surface, and thus may present a novel target for therapeutic interventions in diseases where CD147 functions as a pathogenic factor in cancer, human immunodeficiency virus infection, or rheumatoid arthritis. PPIL2 contains an N-terminal RING-like U-box domain and a C-terminal cyclophilin (Cyp)-like chaperone domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 24580706 247 CLLSIQ---TPtACSVSGYVFCWKCIVSHMKEHGTCPVTHYPISLDDLVRI 294
Cdd:cd16663   5 CALSLQpfeNP-VCTPDGIVFDLLNIVPYLKKYGKNPVTGEPLEAKDLIKL 54

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24580706 243 ECPVCLLSIQTP--TACSvsgYVFCWKCIV-SHMKEHGTCPVTHYPISLDDL 291
Cdd:cd16509   5 ECAICLDSLTNPviTPCA---HVFCRRCICeVIQREKAKCPMCRAPLSASDL 53

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 24580706 244 CPVCLLS-----IQTPTACsvsGYVFCWKCIVSHMKEHGTCPV 281
Cdd:cd16635   7 CPICLNTfrdqaVGTPESC---DHIFCLDCILEWSKNANTCPV 46

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 24580706   244 CPVCLLSIQTP-TACsvsGYVFCWKCIVSHMKEHG---TCP 280
Cdd:pfam13445   1 CPICLELFTDPvLPC---GHTFCRECLEEMSQKKGgkfKCP 38

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 24580706 243 ECPVCLLSIQTP--TACsvsGYVFCWKCIVSHMKE-HGTCPV 281
Cdd:cd16449   2 ECPICLERLKDPvlLPC---GHVFCRECIRRLLESgSIKCPI 40

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 24580706 240 QRGECPVCLLSIQTPTACSVSGYVFCWKCIVSHMKEHGTCPV 281
Cdd:cd16712   2 EEDECPICMDRISNKKVLPKCKHVFCAACIDKAMKYKPVCPV 43

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 24580706 243 ECPVCLLSIQTPtACSVSGYVFCWKCIVSHM--KEHGTCPV 281
Cdd:COG5574 217 KCFLCLEEPEVP-SCTPCGHLFCLSCLLISWtkKKYEFCPL 256

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 24580706 244 CPVCLLSIQTPTACSvSGYVFCWKCIVSHMKEHGTCPVTHYPI 286
Cdd:cd16562   4 CHICLGKVRQPVICS-NNHVFCSSCMDVWLKNNNQCPACRVPI 45

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 24580706 243 ECPVCLLSIQTP--TACsvsGYVFCWKCIVSHMKEHGT---CPV 281
Cdd:cd16745   2 ECNICLDLAQDPvvTLC---GHLFCWPCLHKWLRRQSSqpeCPV 42

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24580706 243 ECPVCLLSIQTpTACSVSGYVFCWKCIVSHMK---EHGTCPVTHYPISLDDLVRIY 295
Cdd:cd16744   2 ECNICLDTAKD-AVVSLCGHLFCWPCLHQWLEtrpNRQVCPVCKAGISRDKVIPLY 56

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); LNX2, also known as numb-binding protein 2, or PDZ domain-containing RING finger protein 1 (PDZRN1), is a PDZ domain-containing RING-type E3 ubiquitin ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. It interacts with contactin-associated protein 4 (Caspr4, also known as CNTNAP4) in a PDZ domain-dependent manner, which modulates the proliferation and neuronal differentiation of neural progenitor cells (NPCs). LNX2 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAF motif for Numb/ Numblike-LNX interaction, and four PDZ domains necessary for the binding of substrates, including ErbB2, RhoC, the presynaptic protein CAST, the melanoma/cancer-testis antigen MAGEB18 and several proteins associated with cell junctions, such as JAM4 and the Coxsackievirus and adenovirus receptor (CAR).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 24580706 244 CPVCLLSIQTP--TACsvsGYVFCWKCIVSHMKEHGTCPV 281
Cdd:cd16780   6 CHICLQPLLQPldTPC---GHTFCFKCLRNFLQEKDFCPL 42

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24580706 235 QQSLpqrgECPVCLLSIQTP--TACsvsGYVFCWKCI---VSHMKEHGTCPVTHYPI---SLDDLVRI 294
Cdd:cd16498  14 QKNL----ECPICLELLKEPvsTKC---DHQFCRFCIlklLQKKKKPAPCPLCKKSVtkrSLQESTRF 74

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 24580706   244 CPVCLLSIQTPTA--CsvsGYVFCWKCIVSHMKE-HG---TCPV 281
Cdd:pfam15227   1 CPICLDYLEKPVSieC---GHSFCLSCINSLQKEpDGeslLCPQ 41